S100A9 exacerbates the inflammation in rosacea via TLR4/MyD88/NF-κB signaling pathway

Rosacea is a chronic inflammatory skin disorder characterized by immune response-dependent erythema and pustules. S100 calcium binding protein A9 (S100A9), a pro-inflammatory alarmin, has been associated with various inflammation-related diseases. However, the specific role of S100A9 in rosacea remains unexplored. Therefore, our objective was to unravel the role of S100A9 in the pathogenesis of rosacea and its underlying molecular mechanisms. Here, we show that expression levels of S100A9 were elevated in both the lesions and serum of PPR patients, as well as in lesions of the LL37-induced rosacea-like mouse model. Moreover, the upregulation of S100A9 was correlated with clinical severity and levels of inflammatory cytokines. Additionally, we demonstrated that S100A9 promoted the production of pro-inflammatory factors in HaCaT cells by activating TLR4/MyD88/NF-κB signaling pathways. Notably, inhibition of S100A9 suppressed the progression of rosacea-like dermatitis and inflammatory responses in the LL37-induced rosacea-like mouse model via TLR4/MyD88/NF-κB signaling pathways. In conclusion, this study illustrated that S100A9 participates in the pathogenesis of rosacea by upregulating TLR4/MyD88/NF-κB signaling pathways, thereby promoting rosacea-associated skin inflammation. These results not only expand our understanding of the potential role of S100A9 in the development of rosacea, but also offers greater insight toward targeted therapies.